Lung transplantation is very successful but limited by availability of donors during the short window between listing and fatal lung failure. This problem is worsened because many potential lung donors are not accepted as borderline lung function might prove fatal in the postoperative period without mechanical support. Extracorporeal Life Support (ECLS) can replace lung function for weeks but is not an appropriate bridge to transplantation. An implantable, total artificial lung (TAL) that could function for 3-6 months would allow more patients to undergo successful lung transplantation, just as the ventricular assist device has been applied to cardiac failure and transplantation. In 2001, we began a ten year project to develop a clinical TAL. We were awarded a bioengineering research partnership (BRP) grant to design and test an implantable total artificial lung (TAL) through the prototype stage. We have completed the goals of that project. Specifically we have developed computer models of device gas exchange and hemodynamics with pulsatile flow to apply to TAL design. We have designed, fabricated, and tested devices, resulting in a prototype (the "Biolung") which meets the specifications for a functional TAL. We developed a servoregulation system to control CO2 clearance by regulating the sweep gas flow. We have routinely implanted the TAL into healthy sheep for 7 days, allowing us to identify the remaining problems which must be solved before clinical trials. These problems are the potential for air embolism, anticoagulation and thrombosis, determining the ideal mode of attachment and TAL blood flow rate, and durability in a 30 day application. With support from renewal of the BRP, we now propose to solve those problems, with the goal of proceeding to clinical trials in five years. Our team of research surgeons, bioengineers, and industry has completed the first half of this project and is ready to bring it to completion. This research team from the University of Michigan includes Robert Bartlett, M.D., a clinician-researcher renowned for his work in ECMO and respiratory failure; Keith Cook, Ph.D., a biomedical engineer with 13 years of experience in the development of total artificial lungs; Jonathan Haft, M.D., a cardiac surgeon with experience in artificial lung testing and clinical heart and lung transplantation; and Ronald Hirschl, M.D., a clinician with 15 years of investigative experience in advanced respiratory support techniques. In addition, Scott Merz, Ph.D., of MC3, Inc., is a biomedical engineer with 16 years experience in the developing artificial lungs and other cardiopulmonary devices. [unreadable] [unreadable] [unreadable]